Method of administration of cabazitaxel compositions

Description

[0001] METHOD OF ADMINISTRATION OF CABAZITAXEL COMPOSITIONS

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives composition for about 30 minutes or less.

[0004] BACKGROUND OF THE INVENTION

[0005] Taxanes are a class of chemotherapy drugs, they are an established treatment regimen for both early and metastatic breast cancer. The mechanism of action of taxanes is to affect microtubules, an essential component of both mitotic spindles and also axonal structures of nerves; axonal damage, therefore, is a common side effect. The solvents used in various taxanes can be an additional source of neurotoxicity; the solvent of paclitaxel, for example, has been shown in preclinical studies to lead to axonal degeneration and demyelination. The neurotoxic effects of taxanes appear to be dose dependent, with higher or more frequent doses associated with higher incidence of neuropathy. Persistent neuropathy can be a doselimiting factor for treatment of breast cancers with taxanes, in turn affecting survival rates.

[0006] JEVTANA® is indicated in combination with prednisone for the treatment of patients with metastatic castration- resista nt prostate cancer previously treated with a docetaxel-containing treatment regimen. The recommended dose of JEVTANA is based on calculation of the Body Surface Area (BSA) and is 20 mg / m2 administered as a one-hour intravenous infusion every three weeks in combination with oral prednisone 10 mg administered daily throughout JEVTANA treatment.

[0007] A dose of 25 mg / m2 can be used in select patients at the discretion of the treating healthcare provider.

[0008] Premedicate at least 30 minutes prior to each dose of JEVTANA with the following intravenous medications to reduce the risk and / or severity of hypersensitivity. ■ antihistamine (dexchlorpheniramine 5 mg, or diphenhydramine 25 mg or equivalent antihistamine),

[0009] ■ corticosteroid (dexamethasone 8 mg or equivalent steroid),

[0010] ■ H2 antagonist.

[0011] Considering the present Jevtana treatment, administering premedication is mandatory for the patients due to the formulation aspects. Further, Jevtana is a hazardous anticancer drug. The medical practioner or paramedical staff needs to follow applicable special handling and disposal procedures. Further, injection single-dose vial requires two dilutions prior to administration. If JEVTANA first diluted solution, or second (final) dilution for intravenous infusion should come into contact with the skin or mucous, immediately and thoroughly wash with soap and water.

[0012] Do not use PVC infusion containers or polyurethane infusions sets for preparation and administration of Jevtana infusion solution.

[0013] Further, Jevtana should not be mixed with any other drugs.

[0014] Considering the Pack insert’s preparation, administration details of JEVTANA, which mentions detailed steps of preparation, dilution, second dilution, and final administration of the drug, which is tedious and time consuming.

[0015] Hence, considering all the above-mentioned drawbacks and tedious process of preparation of the finished product before administration, the present inventors have developed a simple concept of administration to a subject in need thereof cabazitaxel or its derivatives, composition in a short duration of time with no much tedious procedure.

[0016] SUMMARY OF THE INVENTION

[0017] The objective of the present invention relates to a method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition over a period of less than or equal to about 30 minutes or less.

[0018] The method of administration according to the above embodiment, wherein the disease, disorder, or condition is cancer. The method of administration according to above embodiment, wherein the cancer comprises prostate cancer or metastatic castration-resistant prostate cancer, lung cancer, colon cancer, rectum cancer, urinary bladder cancer, melanoma, kidney cancer, renal cancer, oral cavity cancer, pharynx cancer, pancreas cancer, uterine cancer, thyroid cancer, skin cancer, head and neck cancer, cervical cancer, ovarian cancer, or hematopoietic cancer.

[0019] The method of administration according to the above embodiment, wherein cabazitaxel composition is administered over a period of about 25 minutes or less.

[0020] The method of administration according to the above embodiment, wherein cabazitaxel composition is administered over a period of about 20 minutes or less.

[0021] The method of administration according to the above embodiment, wherein cabazitaxel composition is administered over a period of about 15 minutes or less.

[0022] The method of administration according to the above embodiment, wherein cabazitaxel composition is administered over a period of about 10 minutes or less.

[0023] The method of administration according to the above embodiment, wherein cabazitaxel composition is liquid composition, ready to dilute, ready to use, ready to infuse compositions.

[0024] Another aspect relates to the method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof a cabazitaxel or its derivatives composition over a period of about 30 minutes or less; wherein, volume of administration is less than 100 mL. Another aspect relates to the method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof a cabazitaxel or its derivatives composition over a period of about 30 minutes; wherein, volume of administration is 100 mL.

[0025] The method of administration according to the above embodiment, wherein volume of administration is less than 100 mL preferably less than 50 mL.

[0026] The method of administering according to the above embodiment, wherein cabazitaxel composition is administered parenterally.

[0027] The method of administering according to the above embodiment, wherein cabazitaxel composition is administered intravenously.

[0028] DETAILED DESCRIPTION OF THE INVENTION

[0029] The present invention relates to method characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition in a short duration of time with not much tedious procedures.

[0030] The terms used herein is for the purpose of defining specific embodiments only and not intended to be limiting of the application.

[0031] The term “cabazitaxel or its derivatives” includes the compound cabazitaxel, pharmaceutically acceptable salts, esters, isomers, solvates, prodrugs, complexes and hydrates, anhydrous forms thereof, and any polymorphic or amorphous forms or combinations thereof.

[0032] The term “cancer” as used herein includes but not limited to prostate cancer or metastatic castration-resistant prostate cancer, lung cancer, colon cancer, rectum cancer, urinary bladder cancer, melanoma, kidney cancer, renal cancer, oral cavity cancer, pharynx cancer, pancreas cancer, uterine cancer, thyroid cancer, skin cancer, head and neck cancer, cervical cancer, ovarian cancer, hematopoietic cancer, soft tissue sarcoma, leukemia, melanoma, breast cancer, non - small cell lung cancer, leiomyosarcoma, liposarcoma, osteosarcoma, colorectal cancer, mesothelioma, endometrial cancer, and / or similar treatment therapies.

[0033] The term "stable" or "stability" as used herein includes both physical and chemical stability. Stability parameters include but not limited to potency, constant pH value, related substances, and other physico-chemical parameters.

[0034] The term “parenteral” as used herein the compositions are administered by injection, or infusion into the human body. They may be diluted before administration.

[0035] The term “parenteral administration” as used herein may comprise of intramuscular, intraperitoneal, intra-abdominal, subcutaneous, intravenous intradermal, intravitreal, intracerebral, intrathecal, epidural administration. In some embodiments, administration is intravenous.

[0036] The terms “disease” or “disorder” or “condition” are interchangeably used terms, unless otherwise indicated.

[0037] The terms “liquid composition” or “ready to dilute” or “ready to use” or “ready to infuse” as used herein, refers to cabazitaxel composition that is diluted with suitable diluents or physiological solution, 5% dextrose injection, water for injection, 0.9% sodium chloride and the like.

[0038] The term “about” when used in conjugation with a numeral here refers to a range of that numeral ±10%, inclusive. However, alternative concentrations are also expressly deemed suitable for use herein.

[0039] The present invention relates to method characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition in a short duration of time.

[0040] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition over a period of less than or equal to about 30 minutes.

[0041] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel its derivatives, composition over a period of about 25 minutes or less.

[0042] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition over a period of about 20 minutes or less.

[0043] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition over a period of about 15 minutes or less.

[0044] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition over a period of about 10 minutes or less.

[0045] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof a cabazitaxel or its derivatives composition in / for about 30 minutes or less; wherein, volume of administration is less than 100 mL.

[0046] The present invention relates to method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof a cabazitaxel or its derivatives composition in / for about 30 minutes or less; wherein, volume of administration is less than 100 mL, preferably less than 50 mL.

[0047] Further another embodiment relates to, administration of cabazitaxel intravenously as part of an intravenous infusion. Contemplated infusion volumes are preferably less than 100 mL, with volumes such as about 50ml, 30ml, 15 ml or less, with each volume varying about + / -10% or + / -15% being preferred in some embodiments.

[0048] The cabazitaxel compositions are preferably infused intravenously over a period of 30 minutes or less when volume of administration is less than 100 mL.

[0049] The infusible compositions in many aspects of the invention will also preferably include the parenterally acceptable diluents such as 0.9% saline (normal saline, preferred), 0.45% saline (half normal saline, also preferred) or 2.5% dextrose / 0.45% saline. Alternative diluents such as water for injection (WFI) are also contemplated.

[0050] Further another embodiment relates to a method, wherein the method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition in about similar to the existing treatment similar to Jevtana’s product.

[0051] Further another embodiment relates to a method, wherein the method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives, composition in about similar to the existing treatment similar to Jevtana’s product; however, without any tedious multiple dilutions.

[0052] For purposes of the present invention, the step of selecting of patients or Subjects suitable for inclusion in the inventive methods shall be understood to be one of medical or clinical assessment which involves determination of the physical unsuitability of receiving excessive fluid Volumes or other clinical indicia readily apparent to those of ordinary skill.

[0053] The methods include, a) identifying and / or selecting a subject, e.g. a human patient, who is in need of both Cabazitaxel and who has or who would benefit from one or more of fluid; and b) parenterally administering to the subject, preferably by the intravenous route and as a single dose, a Volume of about 100 ml or less of a liquid Cabazitaxel containing composition.

[0054] Another embodiment relates to a method of administration according to the above embodiment, wherein the disease, disorder, or condition is cancer.

[0055] Further, the method of administration according to above embodiment, wherein the cancer comprises prostate cancer / metastatic castration-resistant prostate cancer, lung cancer, colon cancer, rectum cancer, urinary bladder cancer, melanoma, kidney cancer, renal cancer, oral cavity cancer, pharynx cancer, pancreas cancer, uterine cancer, thyroid cancer, skin cancer, head and neck cancer, cervical cancer, ovarian cancer, or hematopoietic cancer.

[0056] Another embodiment relates to composition, wherein the composition is free of surfactants and / or cremophors.

[0057] The present inventors have tried to formulate different compositions and found cyclo-dextrins as a suitable complexing agent for cabazitaxel. Cyclo-dextrins showed better stability and suitability and helped to reduce the duration of administration of composition in shorter duration of time.

[0058] Cyclo-dextrins include but not limited to hydroxypropyl betacyclodextrin, sulfo butylether beta-cyclodextrin,

[0059] Further the composition may optionally further comprise additional components added to improve its pharmaceutical properties. In particular, an acid, a base, and / or a salt can be added to the composition to adjust the pH and the tonicity of the composition. The composition may comprise of HCI, NaOH, organic acids, such as acetic acid, citric acid and the like.

[0060] US 9919053 discloses cabazitaxel composition with differing sulfobutylether beta-cyclodextrin concentrations, however is silent on the shorter administration duration.

[0061] Another embodiment relates to method of administration, wherein cabazitaxel composition is liquid composition, ready to dilute, ready to use, ready to infuse compositions.

[0062] In further embodiments the composition is a sterile liquid aqueous solution suitable for administration by intravenous injection or infusion.

[0063] Table 1 :

[0064] SBE B CD: Sulfo butylether beta-cyclodextrin

[0065] The method of administering according to the above embodiment, wherein cabazitaxel composition is administered parenterally.

[0066] The method of administering according to the above embodiment, wherein cabazitaxel composition is administered intravenously.

[0067] The method of administering according to the above embodiment, wherein cabazitaxel composition is administered parenterally, preferably intravenously, wherein cabazitaxel composition is administered in / for about 30 minutes or less.

[0068] The method of administering according to the above embodiment, wherein cabazitaxel composition is administered parenterally, preferably intravenously, wherein volume of administration is 100 mL or less, administered in / for about 30 minutes or less.

[0069] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.

Claims

We Claim,1. A method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof, cabazitaxel or its derivatives composition over a period of less than or equal to about 30 minutes.

2. The method of administration according to claim 1 , wherein the disease, disorder, or condition is cancer.

3. The method of administration according to claim 2, wherein cancer comprises prostate cancer / metastatic castration-resistant prostate cancer, lung cancer, colon cancer, rectum cancer, urinary bladder cancer, melanoma, kidney cancer, renal cancer, oral cavity cancer, pharynx cancer, pancreas cancer, uterine cancer, thyroid cancer, skin cancer, head and neck cancer, cervical cancer, ovarian cancer, or hematopoietic cancer.

4. The method of administration according to claim 1 , wherein cabazitaxel composition is administered over a period of about 25 minutes or less, over a period of about 20 minutes or less, over a period of about 15 minutes or less, over a period of about 10 minutes or less, over a period of about 5 minutes.

5. The method of administration according to claim 1 , wherein cabazitaxel composition is liquid composition, ready to dilute, ready to use, ready to infuse compositions.

6. A method of administration for treating a disease, disorder, or condition characterized by uncontrolled cell growth, comprising administering to a subject in need thereof cabazitaxel or its derivatives composition over a period of about 30 minutes or less; wherein, the volume administered is less than 100 mL.

7. The method of administration according to claim 6, wherein the volume administered is less than 50 mL over a time period of about 25 minutes or less.

8. The method of administering according to claim 1 to 6, wherein cabazitaxel composition is administered parenterally.

9. The method of administering according to claim 8, wherein cabazitaxel composition is administered intravenously.

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